ß-citronellol alters cell surface properties of Candida albicans to influence pathogenicity related traits.

The pathogenicity of Candida albicans, an opportunistic human fungal pathogen, is attributed to several virulence factors. ß-citronellol is a monoterpenoid present in several plant essential oils. The present study explores the antifungal potential and mode of action of ß-citronellol against C. albicans ATCC 90028 (standard), C. albicans D-27 (FLC-sensitive), and C. albicans S-1 (FLC-resistant). Anti-Candida potential was studied by performing MIC, MFC, growth curves, disc diffusion, spot assay, and WST1 cytotoxic assay. Morphological transition was monitored microscopically in both solid and liquid hyphae inducing media. ß-citronellol inhibits yeast to hyphal transition in both liquid and solid hyphae inducing media. It had a significant inhibitory effect on biofilm formation and secretion of extracellular proteinases and phospholipases. We showed that it has an adverse effect on membrane ergosterol levels and modulates expression of related ERG genes. Expression profiles of selected genes associated with C. albicans pathogenicity displayed reduced expression in treated cells. This work suggests that ß-citronellol inhibits morphological transition in C. albicans and decreases the secretion of hydrolytic enzymes involved in the early stage of infection as well as modulates the expression of associated genes. Pleiotropic phenotype shown by ß-citronellol treated Candida cells suggests various modes of action. Further studies will assess the clinical application of ß-citronellol in the treatment of fungal infections.

Controlling pathogenesis in Candida albicans by targeting Efg1 and Glyoxylate pathway through naturally occurring polyphenols.

Candida albicans has frequently shown resistance to azoles, the commonly used antifungal drugs. Efg1 has dual role under normoxia and hypoxia supporting infection. It is the major regulator of morphogenesis in C. albicans requisite for its pathogenesis. Targeting this protein is expected to render Candida ineffective to undergo filamentation causing virulence. Further the glyoxylate pathway supports the stress resistance and pathogenesis. In the present study an in silico approach and in vitro validation has been performed to find the potential role of polyphenols in controlling hyphal growth in C. albicans. The aspect of changes biome which may provide required niche to the pathogen has been checked which certainly opens the doors towards safe natural polyphenol-based drugs as potent antifungals.

Absence of the glycosyltransferase WcaJ in Klebsiella pneumoniae ATCC13883 affects biofilm formation, increases polymyxin resistance and reduces murine macrophage activation.

Multidrug-resistant Klebsiella pneumoniae has emerged as one of the deadliest opportunistic nosocomial pathogens that forms biofilm for the establishment of chronic K. pneumoniae infections. Herein, we made an attempt to identify the genes involved in biofilm formation in the strain K. pneumoniae ATCC13883. To achieve this, we constructed mini-Tn5 transposon insertion mutants and screened them for biofilm production. We observed that the biofilm formation was enhanced in the mutant where the wcaJ gene was disrupted. WcaJ is the initiating enzyme of colanic acid synthesis and loads the first sugar (glucose-1-P) on the lipid carrier undecaprenyl phosphate. The absence of this glycosyltransferase results in the absence of colanic acid, which renders a non-mucoid phenotype to the mutant. Further, to determine the effect of mucoidy on antibiotic susceptibility, we tested the sensitivity of the strains towards different groups of antibiotics. Unlike the mucoid strains, the resistance of the non-mucoid cells was greater for polymyxins, but less for quinolones. Capsular polysaccharides are known to have a protective effect against phagocytosis, therefore we assessed the role of colanic acid in virulence by conducting infection studies on murine macrophages. Surprisingly, the ΔwcaJ strain was less efficient in macrophage activation and was not readily phagocytosed. Thus, the presence of colanic acid appeared to increase the immunogenicity of K. pneumoniae. Overall, the results indicate that the presence of colanic acid increases the vulnerability of K. pneumoniae towards both polymyxins and macrophages, implying that the mucoid strains are less threatening as compared to their high biofilm forming non-mucoid counterparts.